The kidney contains several distinct epithelia that, in their aggregate function, are responsible for formation of the urine. We are studying the roles of these epithelia in the regulation of the excretion of water, urea, ammonium, bicarbonate, sodium, potassium, and chloride. The general approach is to dissect the epithelia from the kidney and to study their functions in vitro. Experiments in the cortical collecting duct of rat showed that atrial natriuretic factor (ANF) directly inhibits NaCl and fluid absorption. Experiments in rat inner medullary collecting ducts revealed that ANF markedly inhibits vasopressin-stimulated osmotic water permeability by a "post-cyclic AMP" effect. Mathematical modelling studies have demonstrated that ANF effects in the collecting duct system are quantitatively sufficient to account for increases in renal NaCl and fluid excretion. Isolated perfused tubule studies have demonstrated that vasopressin-stimulated urea transport in the rat inner medullary collecting duct is saturable, is inhibited by chemical analogs of urea, is inhibited by phloretin, and is independent of the vasopressin-stimulated water permeability pathway. These results support the view that the urea transport occurs via a specialized urea carrier or channel. Experiments in terminal inner medullary collecting ducts have demonstrated luminal acidification, which is increased by in vivo acidosis or deoxycorticosterone administration and by vasopressin in vivo. Experiments in microdissected rat collecting ducts have demonstrated that the terminal inner medullary collecting duct possesses substantial Na-K-ATPase activity which is enhanced by dietary NaCl restriction or mineralocorticoid administration. Experiments in isolated rabbit papillary surface epithelium have demonstrated that vasopressin reduces passive chloride permeability.